Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detection of DNA variation in cancer is central to the identification of relevant genes and mutations involved in the tumourigenic process. Diverse methods exist for such detection. One category of methods is for the detection of frequent sites for larger DNA alterations in cancer. Such areas may provide clues to the positioning of relevant genes, such as loss of heterozygosity (LOH) as in the case of tumour suppressor genes. Another category of methods is for the detection of single base mutations within specific genes. Frequently, such mutations may obliterate normal protein function. Among the most well-known are DGGE, SSCP, the HOT-method and direct sequencing. The methods for detection of DNA variation of these different levels are discussed. Two methods are presented in more detail. At the large-scale level, two-dimensional DNA fingerprinting has the potential of revealing the extent and location of altered DNA regions. This method is demonstrated using a panel of breast cancer patients. As an example of methods for the small-scale level, a recent development from DGGE, constant denaturant gel electrophoresis (CDGE) is demonstrated. This method has successfully been applied for the detection of mutations in a number of genes. Results with this method in studies of the RB1 gene are given, and its applicability as a screening tool for base mutations is discussed.
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PMID:Detection of DNA variation in cancer. 130 33

In the last ten years considerable progress has been made in small-cell lung carcinoma (SCLC) biology, along with the technical progress made in molecular biology. This progress now allows us to propose a model for the genesis and the development of this type of tumor. Tobacco, the principal causal factor plays a dual role. In bringing about secretion of growth factors by the bronchial epithelia, usually involved in the normal development of lungs, and by functioning autocrinally and paracrinally, it facilitates the occurrence of mitotic mutations. Without directly contributing to cellular transformation, this autocrine functioning also gives a selective advantage to cells going through transformation or immortalization. The procarcinogenic or carcinogenic agents contained in tobacco smoke, whose level of production could be genetically determined, would also contribute to the accumulation of mutations affecting both suppressor genes and oncogenes. Two tumour suppressor genes have been identified: RB1 and P53. At least one other putative tumour suppressor gene has constantly been implied. It lies on the short arm of chromosome 3. There could also be the possibility of detecting subjects susceptible to developing an SCLC, a functional hemizygote still needing evaluation. The activated oncogenes principally belongs to the myc family. Their activation could correspond with the appearance of cellular clones having aggressive behavior independent of growth factors, chemoresistant and more metastatic. SCLC may be distinguished from other malignant lung tumors by a fairly characteristic pattern consisting of the loss of suppressor genes and the activation of oncogenes. The links between the neuroendocrine properties of this type of tumor and its characteristic description are being clarified and will contribute to a better understanding of the relationship between the different types of lung tumors. From this biologic knowledge follow several therapeutic applications under investigation (blocking autocrine loop through anti-GRP antibodies), as well as potential applications (concerning the products of suppressor genes) and possible applications such as prevention oriented towards detection of high-risk subjects.
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PMID:[Biology of small-cell bronchogenic carcinoma: recent advances]. 132 50

Four chromosomal regions were tested for loss of constitutional heterozygosity in primary tumours from 85 Icelandic breast cancer patients. Loss of heterozygosity and other types of gene rearrangements were observed in 37% of informative cases at the retinoblastoma locus, RB1, on chromosome 13q. Allele losses on chromosome 17 were tested with two polymorphic probes on 17p and two on 17q. Loss of heterozygosity or other types of genetic rearrangement were detected in 43.5% of cases on 17p near the p53 gene and 40.5% on 17q. In our study abnormalities at the RB1 locus and on chromosome 17 frequently occurred together, indicating that the coincident inactivation of more than one tumour suppressor gene may, in some cases, play a part in tumour formation. No significant correlation was found between these losses and clinico-histological parameters. Family history of breast cancer was found to be more common among patients with RB1 deletions and this trend was strengthened in cases where there were deletions at both the RB1 locus and on chromosome 17.
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PMID:Loss of heterozygosity at selective sites on chromosomes 13 and 17 in human breast carcinoma. 174 6

A novel class of oncogene has been recognised whose loss-of-function results in the expression of the malignant phenotype. Two examples of such genes are the human retinoblastoma predisposition gene (RB1) and the gene encoding the cellular protein p53. These genes are thought to regulate and limit normal proliferation of cells and, as a consequence, can suppress tumorigenicity when introduced into transformed cells. They are hence frequently described as 'tumour suppressor genes'. Both RB1 and p53 gene products are bound by various transforming early proteins encoded by the DNA tumour viruses SV40, adenovirus and human papilloma virus. It is thought that they are thus sequestered and rendered inactive. Thus, a coherent model is emerging whereby inactivation, either by mutation of sequestration, of these tumour suppressor genes may contribute to natural and experimental carcinogenic processes.
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PMID:The nuclear oncoproteins: RB and p53. 215 36

Soft tissue sarcomas have been examined for alterations in the p53 gene. In six sarcomas, loss or rearrangement of both alleles of this gene was detected while in a further seven sarcomas, point mutation or absence of transcription of the p53 gene was observed. Abnormalities of the p53 gene were found in several classes of soft tissue sarcoma, including leiomyosarcomas, rhabdomyosarcomas and malignant fibrous histiocytomas. Our studies also show that abnormalities of the RB1 suppressor gene and of the p53 gene frequently occur together. These results are consistent with the idea that the p53 gene is a tumour suppressor gene and indicate that coincident inactivation of more than one tumour suppressor gene may, in some cases, be required for tumour development.
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PMID:Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene. 221 56

The first human tumour suppressor gene, the Retinoblastoma Susceptibility gene (RB1) was first demonstrated in retinoblastoma, a rare paediatric eye tumour which has been studied extensively over the last century. Genetic studies of retinoblastoma have yielded unique insights into familial cancer syndromes and the mechanisms of oncogenesis by tumour suppressor genes such as the RB1 gene. In this view, we will summarize past research into the genetics of retinoblastoma that led to the discovery of the RB1 gene and discuss the influence these results have had on the field of cancer research. In addition, we will discuss current research into RB1 as it relates to cancer and its potential for new therapies.
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PMID:The retinoblastoma gene and its significance. 807 36

Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observation suggests the location of a gene important in leukaemogenesis. A series of 68 BCLL tumours have been analysed for allele loss using a series of probes from 13q14. Using intragenic polymorphic markers from the retinoblastoma predisposition gene LOH was observed in 25% of tumours including 3/6 showing cytogenetically obvious deletions of the 13q14 region and 3/6 showing translocations involving 13q14. However, three deletions with proximal breakpoints in 13q14 did not show allele loss, demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with structural rearrangements of 13q14 and 75% of tumours with an apparently normal karyotype. 50% of these tumours showed homozygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimum region of overlap for homozygous deletions is approximately 1 Mbp around the D13S25 locus.
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PMID:Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia. 813 33

Roughly 25% of human B-cell chronic lymphocytic leukaemias (CLL) are characterized by a chromosomal lesion involving 13q14. This region contains the retinoblastoma gene (RB1). We have used a variety of techniques to determine whether RB1 or some other locus is the critical region in 11 cases of low grade B-cell malignancy (mainly CLL), all with deletions or translocations involving 13q14. In all cases, except the one with minimal disease, there was deletion or a structural lesion in the region of D13S25, with at least 4 cases showing homozygous disruption. We conclude that D13S25 lies close to a tumour suppressor locus whose inactivation contributes to the initiation or progression of low grade B-cell malignancy. This locus is located at least 530 kilobases telomeric to RB1.
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PMID:Evidence for a new tumour suppressor locus (DBM) in human B-cell neoplasia telomeric to the retinoblastoma gene. 849 Jun 58

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
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PMID:Allele imbalance at tumour suppressor loci during the indolent phase of follicle centre cell lymphoma. 872 37

The occurrence of retinoblastoma gene abnormalities in a large subset of various malignancies suggests an important role for this tumour suppressor gene in carcinogenesis, but this varies considerably from one tumour type to another and results in patients with acute myeloid leukaemia (AML) have been controversial. We analysed 106 AML patients and 18 normal controls for RB1 gene rearrangements and 86 AML patients for RB protein (pRB) expression. Southern blot analysis detected no gross gene rearrangements, but several restriction enzyme polymorphisms were observed. By Western blot analysis, 20 patients (23%) had no detectable pRB protein and seven (8%) had truncated pRB bands. Discordance between the DNA and protein data suggests that there may be minor deletions and point mutations in the RB1 gene or abnormalities in the proteins regulating the expression of pRB. No significant differences in the frequency of attainment of complete remission or length of survival were observed between patients with normal and abnormal pRB.
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PMID:The retinoblastoma gene (rb1) in acute myeloid leukaemia: analysis of gene rearrangements, protein expression and comparison of disease outcome. 875 95


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